ICGEB-Emory Vaccine Center, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi, India.
J Virol. 2021 Nov 9;95(23):e0061021. doi: 10.1128/JVI.00610-21. Epub 2021 Sep 15.
Plasmablasts represent a specialized class of antibody-secreting effector B cells that transiently appear in blood circulation following infection or vaccination. The expansion of these cells generally tends to be massive in patients with systemic infections such as dengue or Ebola that cause hemorrhagic fever. To gain a detailed understanding of human plasmablast responses beyond antibody expression, here, we performed immunophenotyping and RNA sequencing (RNA-seq) analysis of the plasmablasts from dengue febrile children in India. We found that plasmablasts expressed several adhesion molecules and chemokines or chemokine receptors that are involved in endothelial interactions or homing to inflamed tissues, including skin, mucosa, and intestine, and upregulated the expression of several cytokine genes that are involved in leukocyte extravasation and angiogenesis. These plasmablasts also upregulated the expression of receptors for several B-cell prosurvival cytokines that are known to be induced robustly in systemic viral infections such as dengue, some of which generally tend to be relatively higher in patients manifesting hemorrhage and/or shock than in patients with mild febrile infection. These findings improve our understanding of human plasmablast responses during the acute febrile phase of systemic dengue infection. Dengue is globally spreading, with over 100 million clinical cases annually, with symptoms ranging from mild self-limiting febrile illness to more severe and sometimes life-threatening dengue hemorrhagic fever or shock, especially among children. The pathophysiology of dengue is complex and remains poorly understood despite many advances indicating a key role for antibody-dependent enhancement of infection. While serum antibodies have been extensively studied, the characteristics of the early cellular factories responsible for antibody production, i.e., plasmablasts, are only beginning to emerge. This study provides a comprehensive understanding of the transcriptional profiles of human plasmablasts from dengue patients.
浆母细胞是一种特殊的分泌抗体效应 B 细胞，在感染或接种疫苗后会短暂出现在血液循环中。在引起出血热的全身性感染（如登革热或埃博拉）患者中，这些细胞通常会大量扩增。为了更详细地了解人类浆母细胞的反应，除了抗体表达之外，我们还对来自印度登革热发热儿童的浆母细胞进行了免疫表型和 RNA 测序（RNA-seq）分析。我们发现浆母细胞表达了几种参与内皮细胞相互作用或归巢到炎症组织（包括皮肤、黏膜和肠道）的黏附分子和趋化因子或趋化因子受体，并上调了几种参与白细胞渗出和血管生成的细胞因子基因的表达。这些浆母细胞还上调了几种 B 细胞生存素细胞因子的受体表达，这些细胞因子在全身性病毒感染（如登革热）中被强烈诱导，其中一些在表现出血和/或休克的患者中通常比表现为轻度发热感染的患者相对较高。这些发现提高了我们对登革热全身性感染急性发热期人类浆母细胞反应的理解。 登革热在全球范围内传播，每年有超过 1 亿例临床病例，症状从轻度自限性发热疾病到更严重、有时危及生命的登革出血热或休克不等，尤其是在儿童中。登革热的病理生理学很复杂，尽管有许多进展表明抗体依赖性增强感染起着关键作用，但仍未得到很好的理解。虽然血清抗体已被广泛研究，但负责抗体产生的早期细胞工厂（即浆母细胞）的特征才刚刚开始出现。这项研究提供了对登革热患者浆母细胞转录谱的全面了解。
